About five years ago a pair of scientists at the Gladstone Institutes — Robert Mahley and Yadong Huang — had seen enough clinical failures in Alzheimer’s drug research to urge a change in strategy. If the classic approach on leeching amyloid-beta out of the brain was producing only colossal failure, they said, why not zero in on a key genetic trigger linked to a well-defined risk of developing the disease?
Out of that work, about three years later, came a stealth biotech in South San Francisco backed by Orbimed. A team and syndicate of investors came together, including the venture arms of some of the major players interested in blazing a new path in the field of neurodegeneration. For two years, they’ve been quietly laboring on preclinical work aimed at ApoE4 — a prime culprit in the disease — with the help of Mahley and Huang. And today they’re having a coming out party of sorts, with $63 million in venture cash to celebrate and plans to launch the clinical work that will be needed to prove they may be on to something.
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The fledgling has some backers with very deep pockets and a patient attitude about trying something new. Alongside Orbimed you’ll find Novo Holding A/S, Johnson & Johnson Innovation — JJDC, Novartis Venture Fund and Osage University Partners. New investors include Lilly Asia Ventures and Sutter Hill Ventures. Insiders won’t overlook the four corporate venture arms in the group.
“The concept was to start a new company focused on genetically defined patient populations in neurodegenerative diseases,” says Leon Chen, an Orbimed partner who’s managing the 16-member scientific team. Eventually, Chen will step aside and go back to company creation after the backers find a permanent CEO.
Their research squad has been tinkering away on new small molecule therapies that can restructure ApoE4, linked to a much, much higher risk of developing the disease, into a protein that mimics ApoE3, a variation that might well defuse a genetic driver of the disease.
Like a lot of startup CEOs, Chen is leery about offering a timeline for getting into the clinic with their first drug. The investors have put $46 million into the company and another $17 million tranche is waiting to finish assembling the preclinical pipeline with multiple drug candidates for both Alzheimer’s and Parkinson’s disease. Then they can start human testing in search of that first look at human proof-of-concept data.
Alzheimer’s is one of the toughest targets in biopharma. Late-stage pivotal studies have been big and monumentally expensive. A genetic approach — a notion that also helped inspire Ryan Watts’ group at Denali, a South San Francisco player operated by a bunch of Genentech vets — could be done with a smaller patient population, much more narrowly defined. In some of the early Alzheimer’s studies, researchers didn’t have the diagnostic tools available to even make sure all the patients in their studies actually had the disease. It was a sure fire way to worsen the odds against success.
Chen quickly countered my suggestion that a drug targeting the structure of ApoE4 would have to be used years ahead of any symptoms. Their work, he says, suggests that a drug like that could have a significant impact at the early stage of disease development, exactly where most investigators are focused these days, before Alzheimer’s wipes out memory.
It’s a bold plan. And they have the money to put it to a critical test.
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